Insulin Resistance As Putative Cause of Chronic Renal Transplant Dysfunction

Transplantation is the preferred organ replacement therapy for most patients with end-stage renal disease. Despite impressive improvements over recent years in the treatment of acute rejection, approximately half of all grafts will loose function within 10 years after transplantation. Chronic renal transplant dysfunction, also known as transplant atherosclerosis, is a leading cause of late allograft loss. To date, no specific treatment for chronic renal transplant dysfunction is available. Although its precise pathophysiology remains unknown, it is believed that it involves a multifactorial process of alloantigen-dependent and alloantigen-independent risk factors. Obesity, posttransplant diabetes mellitus, dyslipidemia, hypertension, and proteinuria have all been identified as alloantigen-independent risk factors. Notably, these recipient-related risk factors are well-known risk factors for cardiovascular disease, which cluster within the insulin resistance syndrome in the general population. Insulin resistance is considered the central pathophysiologic feature of this syndrome. It is therefore tempting to speculate that it is insulin resistance that underlies the recipient-related risk factors for chronic renal transplant dysfunction. Recognition of insulin resistance as a central feature underlying many, if not all, recipient-related risk factors would not only improve our understanding of the pathophysiology of chronic renal transplant dysfunction, but also stimulate development of new treatment and prevention strategies.